title: Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use.
abstract: BACKGROUND
  The effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA. This study examined the effects of high versus low dose FO in early RA employing a 'treat-to-target' protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
  
  
  METHODS
  Patients with RA <12 months' duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.
  
  
  RESULTS
  In the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti-cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.
  
  
  CONCLUSIONS
  FO was associated with benefits additional to those achieved by combination 'treat-to-target' DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: James
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Llewellyn D
authors.initials: LD
authors.lastname: Spargo
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Metcalf
authors.affiliation: Discipline of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sullivan
authors.affiliation: Rheumatology Unit, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
authors.forename: Maureen
authors.initials: M
authors.lastname: Rischmueller
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Flabouris
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Mihir D
authors.initials: MD
authors.lastname: Wechalekar
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Lee
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001799:Blood Sedimentation; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D061345:Early Medical Intervention; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D012460:Sulfasalazine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D005395:Fish Oils; D007555:Isoxazoles; D004281:Docosahexaenoic Acids; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D015118:Eicosapentaenoic Acid; D000077339:Leflunomide; D008727:Methotrexate
keywords: Combination DMARDs; Fish Oil; Rheumatoid Arthritis; Treat to Target